Two species of mutans streptococci, Streptococcus mutans and Streptococcus sobrinus, are considered the primary etiological agents of human dental caries. Although both species are highly cariogenic, the majority of studies have been carried out with S. mutans; primarily because of the strong association of S. mutans with caries in developed nations, but also because of the relative ease of genetic manipulation of S. mutans compared to S. sobrinus. It is well known that S. mutans is inherently more acid resistant than many other oral bacteria and is able to mount an adaptive acid tolerance response (ATR) (Belli and Marquis, 1991; Hamilton and Buckley, 1991). Previously, S. sobrinus, although intrinsically acid tolerant, was considered to lack the capacity to mount an ATR (Svensater et al., 1997). Recently, our laboratory conducted a more detailed analysis of the responses of S. sobrinus to environmental acidification (Nascimento et al., 2004). Our results indicated that S. sobrinus was in fact capable of developing a vigorous ATR during cultivation at acidic pH. Interestingly, our data indicated that there are critical differences in the molecular mechanisms of acid adaptation by S. sobrinus and S. mutans. Among the more intriguing findings, expression of the F-ATPase of S. sobrinus was not enhanced by growth in acidic conditions, as it is in many other organisms, and expression of the glucose-specific phosphoenolpyruvate sugar: phosphotransferase system (PTS), which in S. mutans is repressed during growth at low pH, was two-fold higher in S. sobrinus cells grown at pH 5.0 compared to pH 7.0-grown cells (Nascimento et al., 2004). The goal of this application is to extend our investigations on the S. sobrinus ATR by pursuing the following specific aims: (i) Identification and characterization of acid tolerance responses of S. sobrinus, and (ii) analysis of the acid tolerance properties of a S. sobrinus strain lacking the glucose-specific enzyme II (EIIGIc) of the PTS. [unreadable] [unreadable] [unreadable]